【整理】美國FDA分析方法驗證指南中英文對照

1、美國FDA分析方法驗證指南中英文對照二 HYPERLINK :/ antpedia /batch mon.php?action=viewspace&op=up&itemid=27524&uid=2541 上一篇 / HYPERLINK :/ antpedia /batch mon.php?action=viewspace&op=next&itemid=27524&uid=2541 下一篇 2021-01-05 10:44:15 / 個人分類： HYPERLINK :/ antpedia /?uid-2541-action-spacelist-type-blog-itemtypeid-773 G

2、MP/GLP HYPERLINK :/ antpedia /?uid-2541-action-viewspace-itemid-27524 l xspace-tracks#xspace-tracks 查看( 1076 ) / HYPERLINK :/ antpedia /?uid-2541-action-viewspace-itemid-27524 l xspace-itemreply#xspace-itemreply 評論( 2 ) / HYPERLINK :/ antpedia /?uid-2541-action-viewspace-itemid-27524 l xspace-itemfo

3、rm#xspace-itemform 評分( 0 / 0 ) III. TYPES OF ANALYTICAL PROCEDURESA. Regulatory Analytical ProcedureA regulatory analytical procedure is the analytical procedure used to evaluate a defined characteristic of the drug substance or drug product. The analytical procedures in the U.S. Pharmacopeia/Nation

4、al Formulary (USP/NF) are those legally recognized under section 501(b) of the Food, Drug, and Cosmetic Act (the Act) as the regulatory analytical procedures for compendial items. For purposes of determining compliance with the Act, the regulatory analytical procedure is used.III HYPERLINK javascrip

5、t:; t _self 分析方法的類型A. 法定分析方法法定分析方法是被用來評估原料藥或制劑的特定性質(zhì)的。USP/NF中的分析方法是法定的用于藥典工程 HYPERLINK javascript:; t _self 檢測的分析方法。為了確認(rèn)符合法規(guī)，需使用法定分析方法。B. Alternative Analytical ProcedureAn alternative analytical procedure is an analytical procedure proposed by the applicant for use instead of the regulatory analytic

6、al procedure. A validated alternative analytical procedure should be submitted only if it is shown to perform. equal to or better than the regulatory analytical procedure.B. 替代分析方法替代分析方法是申請者提出用于代替法定分析方法的分析方法。只有當(dāng)一替代分析方法相當(dāng)于或優(yōu)于法定分析方法時，才可以 HYPERLINK javascript:; t _self 應(yīng)用驗證過的替代分析方法。If an alternative an

7、alytical procedure is submitted, the applicant should provide a rationale for its inclusion and identify its use (e.g., release, stability testing), validation data, and comparative data to the regulatory analytical procedure.如果提交了替代分析方法，申請者還應(yīng)當(dāng)提供其理由，并標(biāo)明其用途如，放行，穩(wěn)定性實驗，驗證資料及其與法定分析方法的比照資料。C. Stability-I

8、ndicating AssayA stability-indicating assay is a validated quantitative analytical procedure that can detect the changes with time in the pertinent properties of the drug substance and drug product.C. 穩(wěn)定性指示分析穩(wěn)定性指示分析是能檢測出原料藥或制劑的某些性質(zhì)隨著時間的延長而出現(xiàn)的變化的定量分析方法。A stability-indicating assay accurately measures

9、 the active ingredients, without interference from degradation products, process impurities, excipients, or other potential impurities。穩(wěn)定性指示分析能不受降解產(chǎn)物，工藝雜質(zhì)，賦形劑或其它潛在雜質(zhì)的影響而準(zhǔn)確 HYPERLINK javascript:; t _self 測定其中的活性成分。If an applicant submits a non-stability-indicating analytical procedure for release tes

10、ting, then an analytical procedure capable of qualitatively and quantitatively monitoring the impurities, including degradation products, should complement it. Assay analytical procedures for stability studies should be stability-indicating, unless scientifically justified.如果申請者遞交了用于放行檢測的非穩(wěn)定性指示分析方法，

11、那么應(yīng)當(dāng)要有能定性和定量地監(jiān)測雜質(zhì)，包括降解產(chǎn)物，的分析方法對其進行補充。穩(wěn)定性 HYPERLINK javascript:; t _self 試驗中所用的 HYPERLINK javascript:; t _self 含量分析方法應(yīng)當(dāng)要有穩(wěn)定性指示能力，除非有 HYPERLINK javascript:; t _self 科學(xué)的理由能證明其合理性。IV. REFERENCE STANDARDSA. Types of StandardsA reference standard (i.e., primary standard) may be obtained from the USP/NF or

12、 other official sources (e.g., CBER, 21 CFR 610.20). If there are questions on whether a source of a standard would be considered by FDA to be an official source, applicants should contact the appropriate chemistry review staff. When there is no official source, a reference standard should be of the

13、 highest possible purity and be fully characterized.IV HYPERLINK javascript:; t _self 標(biāo)準(zhǔn)品A標(biāo)準(zhǔn)品的類型可以從USP/NF處或其它官方(比方說，CBER，21CFR 610.20)獲得標(biāo)準(zhǔn)品 (也就是一級對照品)。如果不能確定一標(biāo)準(zhǔn)品的來源是否會被FDA認(rèn)為是官方來源，申請者應(yīng)當(dāng)要向適當(dāng)?shù)?HYPERLINK javascript:; t _self 化學(xué)評審人員咨詢。如果沒有官方來源，那么被用來作標(biāo)準(zhǔn)品的物質(zhì)應(yīng)當(dāng)要有盡可能高的純度，并得到充分界定。A working standard (i.e., in-

14、house or secondary standard) is a standard that is qualified against and used instead of the reference standard.工作對照品 (也就是內(nèi)部標(biāo)準(zhǔn)品或二級標(biāo)準(zhǔn)品)是根據(jù)一級對照品標(biāo)定的，并用來代替一級對照品的。B. Certificate of AnalysisA certificate of analysis (COA) for reference standards from non-official sources should be submitted in the section

15、 of the application on analytical procedures and controls. For standards from official sources, the user should ensure the suitability of the reference standard. The standard should be stored correctly and used within the established use interval.B分析報告單對于非官方標(biāo)準(zhǔn)品，在申請的分析方法和控制章節(jié)中應(yīng)當(dāng)要提供該標(biāo)準(zhǔn)品的分析報告單。對于從官方獲得的

16、標(biāo)準(zhǔn)品，用戶應(yīng)當(dāng)要確保標(biāo)準(zhǔn)品的適用性。應(yīng)當(dāng)正確儲存標(biāo)準(zhǔn)品并在已確定的時間段內(nèi)使用該標(biāo)準(zhǔn)品。C. Characterization of a Reference StandardReference standards from USP/NF and other official sources do not require further characterization. A reference standard that is not obtained from an official source should be of the highest purity that can be ob

17、tained by reasonable effort, and it should be thoroughly characterized to ensure its identity, strength, quality, purity, and potency.C標(biāo)準(zhǔn)品的界定從USP/NF及其它官方來源獲得的標(biāo)準(zhǔn)品是不需要進一步界定的。非官方對照品要有盡可能高的純度，并進行充分地界定以確保其結(jié)構(gòu)，劑量，質(zhì)量，純度和效力。The qualitative and quantitative analytical procedures used to characterize a referen

18、ce standard are expected to be different from, and more extensive than, those used to control the identity, strength, quality, purity, and potency of the drug substance or the drug product. Analytical procedures used to Draft Not for Implementation characterize a reference standard should not rely s

19、olely on comparison testing to a previously designated reference standard.用于界定標(biāo)準(zhǔn)品的定性和定量分析方法應(yīng)當(dāng)要不同于用于控制原料藥或制劑的結(jié)構(gòu)，劑量，質(zhì)量，純度和效力的分析方法，要比它們更深入。用于標(biāo)準(zhǔn)品界定的分析方法不應(yīng)僅僅是和先前的指定標(biāo)準(zhǔn)品進行比擬實驗。Generally, this characterization information should include:A brief description of the manufacture of the reference standard, if th

20、e manufacturing process differs from that of the drug substance. Any additional purification procedures used in the preparation of the reference standard should be described.一般來說，界定資料應(yīng)當(dāng)要包括：標(biāo)準(zhǔn)品的簡單工藝描述，如果其生產(chǎn)工藝是否于其相應(yīng)的原料藥的話。應(yīng)當(dāng)要表達制備標(biāo)準(zhǔn)品時所用的補充精制過程。Legible reproductions of the relevant spectra, chromatogram

21、s, thin-layer chromatogram (TLC) photographs or reproductions, and other appropriate instrumental recordings. Data establishing purity. The data should be obtained by using appropriate tests, such as TLC, gas chromatography (GC), high-pressure liquid chromatography (HPLC), phase solubility analysis,

22、 appropriate thermometric analytical procedures, and others as necessary.相關(guān) HYPERLINK javascript:; t _self 光譜圖， HYPERLINK javascript:; t _self 色譜圖，TLC照片及其它儀器輸出的清晰復(fù)印件。建立純度的資料。應(yīng)當(dāng)要應(yīng)用適當(dāng)?shù)臋z測方法來獲得這些資料，比方說TLC，GC，HPLC，相溶解分析，適當(dāng)?shù)臒岱治龇椒捌渌匾姆治龇椒?。Appropriate chemical attribute information, such as structural for

23、mula, empirical formula, and molecular weight. Information to substantiate the proof of structure should include appropriate analytical tests, such as elemental analysis, infrared spectrophotometry (IR), ultraviolet spectrophotometry (UV), nuclear magnetic resonance spectroscopy (NMR), and mass spec

24、trometry (MS), as well as applicable functional group analysis. Detailed interpretation of the test data in support of the claimed structure should be provided.適當(dāng)?shù)幕瘜W(xué)性質(zhì)資料，比方結(jié)構(gòu)式，經(jīng)驗式和分子量等。結(jié)構(gòu)確證資料應(yīng)當(dāng)要包括適當(dāng)?shù)姆治鰷y試，比方元素分析，IR，UV,NMR和MS，及適用的官能團分析。還應(yīng)當(dāng)要提供具體的結(jié)構(gòu)解析資料。A physical description of the material, including

25、its color and physical form. Appropriate physical constants such as melting range, boiling range, refractive index, dissociation constants (pK values), and optical rotation. A detailed description of the analytical procedures used to characterize the reference standard.物理性質(zhì)的描述，包括顏色和物理形態(tài)。 適當(dāng)?shù)奈锢沓?shù)，比方說

26、熔程，沸程，折射率，離解常數(shù)(pK值)和旋光度。用于界定標(biāo)準(zhǔn)品的分析程序的詳細(xì)表達。For biotechnological/biological product reference standards, the recommendations on characterization information above may apply and should be considered. However, additional and/or different tests would be important to assess physicochemical characteristics

27、, structural characteristics, biological activity, and/or immunochemical activity.至于 HYPERLINK javascript:; t _self 生物技術(shù)/生物產(chǎn)品的標(biāo)準(zhǔn)品，應(yīng)當(dāng)要考慮上述建議，可能可以應(yīng)用。然而，其它確定物理化學(xué)性質(zhì)，結(jié)構(gòu)特性，生物活性和/或免疫化學(xué)活性的補充檢測和/或其它檢測將是非常重要的。Physicochemical determinations may include isoform, electrophoretic, and liquid chromatographic patte

28、rns, as well as spectroscopic profiles. Structural characterization may include a determination of amino acid sequence, amino acid composition, peptide map, and carbohydrate structure. Biological and/or immunochemical activity should be assessed using the same analytical procedures used to determine

29、 product potency.物理化學(xué)性質(zhì)包括異構(gòu)體， HYPERLINK javascript:; t _self 電泳和 HYPERLINK javascript:; t _self 液相色譜行為及光譜性質(zhì)等。結(jié)構(gòu)界定可能包括 HYPERLINK javascript:; t _self 氨基酸序列，氨基酸組成，縮氨酸圖和碳水結(jié)構(gòu)。確定生物和/或免疫化學(xué)活性的分析方法應(yīng)當(dāng)要和用來確定產(chǎn)品效力的分析方法一樣。These can include animal-based, cell culture-based, biochemical, or ligand/receptor-binding

30、 assays. While these tests may be needed for complete characterization of certain reference standards, specific recommendations for validation of biological and immunochemical tests are not contained in this guidance document.這些分析方法可以包括基于動物的， HYPERLINK javascript:; t _self 細(xì)胞培養(yǎng)的，生物化學(xué)的或配位體/接受體螯合的分析方法

31、。如果這些檢測需用于某些標(biāo)準(zhǔn)品的界定，生物和免疫化學(xué)檢測的分析 HYPERLINK javascript:; t _self 方法驗證方面的特殊建議并不在本指南的范圍之內(nèi)。V. METHODS VALIDATION FOR INDsFor an investigational new drug, sufficient information is required in each phase of an investigation to ensure proper identification, quality, purity, strength, and/or potency. The am

32、ount of information on analytical procedures and methods validation necessary will vary with the phase of the investigation (21 CFR 312.23(a)(7).VIND中的分析方法驗證對于IND而言，每個階段的研究都需要有足夠的資料以確保適宜的認(rèn)定，質(zhì)量，純度，劑量和/或效力。所需的分析方法和方法驗證方面的資料會隨著研究的階段變化而變化(21CFR312.23(a)(7)。For general guidance on analytical procedures a

33、nd methods validation information to be submitted for phase 1 studies, sponsors should refer to the FDA guidance for industry on Content and Format of Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs, Including Well- Characterized, Therapeutic, Biotechnology-Derived Products

34、 (November 1995).關(guān)于在第1階段研究所需提交的分析方法和方法驗證資料方面的指南，發(fā)起人可以參考FDA的指南：藥品包括結(jié)構(gòu)確定的，有療效的，生物 HYPERLINK javascript:; t _self 技術(shù)產(chǎn)品第1階段研究的IND申請的內(nèi)容和格式1995年11月。General guidance regarding analytical procedures and methods validation information to be submitted for phase 2 or phase 3 studies will be provided in the FDA

35、 guidance for industry INDs for Phase 2 and 3 Studies of Drugs, Including Specified Therapeutic Biotechnology-Derived Products, Chemistry, Manufacturing, and Controls Content and Format, when finalized (draft guidance published April 1999).第2和第3階段研究所需提交的分析方法和方法驗證資料方面的指南，發(fā)起人將可以參考FDA的指南：藥品包括結(jié)構(gòu)確定的，有療效的

36、，生物技術(shù)產(chǎn)品第1階段研究的IND申請的CMC內(nèi)容和格式草案，1999年4月。All analytical procedures should be fully developed and validation completed when the NDA, ANDA, BLA, or PLA is submitted.在遞交NDA，ANDA，BLA或PLA時，所有的分析方法都應(yīng)當(dāng)要開發(fā)出來，并得到驗美國FDA分析方法驗證指南中英文對照三 HYPERLINK :/ antpedia /batch mon.php?action=viewspace&op=up&itemid=27526&uid=2

37、541 上一篇 / HYPERLINK :/ antpedia /batch mon.php?action=viewspace&op=next&itemid=27526&uid=2541 下一篇 2021-01-05 10:58:48 / 個人分類： HYPERLINK :/ antpedia /?uid-2541-action-spacelist-type-blog-itemtypeid-773 GMP/GLP HYPERLINK :/ antpedia /?uid-2541-action-viewspace-itemid-27526 l xspace-tracks#xspace-track

38、s 查看( 869 ) / HYPERLINK :/ antpedia /?uid-2541-action-viewspace-itemid-27526 l xspace-itemreply#xspace-itemreply 評論( 1 ) / HYPERLINK :/ antpedia /?uid-2541-action-viewspace-itemid-27526 l xspace-itemform#xspace-itemform 評分( 0 / 0 ) VI. CONTENT AND FORMAT OF ANALYTICAL PROCEDURES FOR NDAs, 230ANDAs,

39、BLAs, AND PLAsAny analytical procedure submitted in an NDA, ANDA, BLA, or PLA should be described in sufficient detail to allow a competent analyst to reproduce the necessary conditions and obtain results comparable to the applicant=s. Aspects of the analytical procedure that require special attenti

40、on should be described.VINDA，ANDA，BLA和PLA中 HYPERLINK javascript:; t _self 分析方法的內(nèi)容和格式NDA，ANDA，BLA和PLA中所提交的任一分析方法都應(yīng)當(dāng)要有詳細(xì)的描述，以使合格的分析人員能重現(xiàn)出所需的實驗條件并獲得和申請者相當(dāng)?shù)膶嶒灲Y(jié)果。應(yīng)當(dāng)要表達分析方法中需要特殊注意的地方。If the analytical procedure used is in the current revision of the USP/NF or other FDA recognized standard references (e.g.

41、, AOAC International Book Of Methods) and the referenced analytical procedure is not modified, a statement indicating the analytical procedure and reference may be provided rather than a description of the method (21 CFR 211.194).如果所用的分析方法是USP/NF或其它FDA認(rèn)可參考文獻如，中且所參考的分析方法未經(jīng)過修改的話，那么需提供該分析方法的參引，而不用提供該分析

42、方法的描述21 CFR 211.194。A description of analytical procedures from any other published sources should be provided, because the referenced sources may not be readily accessible to the reviewer.對于從其它公開發(fā)表的文獻上獲得的分析方法，應(yīng)當(dāng)要對其進行表達，因為評審官可能并不能很方便的獲得這些文獻。分析方法描述中需要包括的典型內(nèi)容如下所示：A. PrincipleA statement of the princip

43、le of the analytical procedure should be included. For example, separation is based on isocratic reversed phase HPLC with detection by UV.A根本方法HPLC進行 HYPERLINK javascript:; t _self 別離的， HYPERLINK javascript:; t _self 檢測器為UV檢測器。B. SamplingThe number of samples (e.g., vials, tablets) selected, how the

44、y are used (i.e., as individual or composite samples), and the number of replicate analyses per sample should be described.B取樣需要表達的有：所選樣品的數(shù)目比方，瓶，片等，它們是如何使用的也就是，單獨的或是混合樣品，每個樣品分析的重復(fù)次數(shù)。C. Equipment and Equipment ParametersA listing of all equipment (e.g., instrument type, detector, column type, dimensi

45、ons) should be included, as well as a list of equipment parameters (e.g., flow rate, temperatures, run time, wavelength settings). A drawing representing the experimental configuration (e.g., illustrating positions for a spray pattern analytical procedure) should be provided, when appropriate.C儀器和儀器

46、參數(shù)需要表達的有：儀器列表比方，儀器類型，檢測器，柱子類型，尺寸等和儀器參數(shù)比方，流速，溫度，運行時間和設(shè)定波長等。如果必要的話，還要提供實驗結(jié)構(gòu)示意圖比方，闡述噴灑式分析方法的位置。D. ReagentsA list of reagents and their grades (e.g., USP/NF, American Chemical Society (ACS) Analytical Reagent) should be included. If in-house or modified commercial reagents are used, directions for their

47、 preparation should be included. Unstable or potentially hazardous reagents should be identified, and storage conditions, directions for safe use, and usable shelf life for these reagents should be specified.D HYPERLINK javascript:; t _self 試劑需要表達的有：試劑列表及其相應(yīng)的規(guī)格比方：USP/NF， HYPERLINK javascript:; t _se

48、lf 美國 HYPERLINK javascript:; t _self 化學(xué)社ACS分析試劑。如果使用的是自制試劑或更改正的商業(yè)試劑，那么應(yīng)當(dāng)要有其制備方法。對于不穩(wěn)定的或有潛在危險的試劑，應(yīng)標(biāo)明其儲存條件， HYPERLINK javascript:; t _self 平安使用說明和使用周期。E. System Suitability TestingSystem suitability test parameters and acceptance criteria are based on the concept that the equipment, electronics, analy

49、tical operations, and samples to be analyzed constitute an integrated system. System suitability testing ensures that the system is working properly at the time of analysis. Appropriate system suitability criteria should be defined and included in the analytical procedure.E系統(tǒng)適應(yīng)性實驗系統(tǒng)適應(yīng)性實驗參數(shù)和合格 HYPERL

50、INK javascript:; t _self 標(biāo)準(zhǔn)是建立根底是：儀器，電子元件，分析操作和待測樣品是個不可分割的整體。系統(tǒng)適應(yīng)性實驗確保系統(tǒng)在樣品分析的時候能很好地運行。在分析方法中應(yīng)當(dāng)要包括適當(dāng)?shù)南到y(tǒng)適應(yīng)性合格標(biāo)準(zhǔn)。All chromatographic analytical procedures should include system suitability testing and criteria. Parameters typically used in system suitability evaluations are defined and discussed in th

51、e CDER reviewer guidance on Validation of Chromatographic Methods (November 1994).所有的 HYPERLINK javascript:; t _self 色譜分析方法都應(yīng)當(dāng)要有系統(tǒng)適應(yīng)性實驗及相應(yīng)的合格標(biāo)準(zhǔn)。CDER評審官指南1994年11月對用于評估系統(tǒng)適應(yīng)性的典型參數(shù)進行了定義和討論。System suitability testing is recommended as a component of any analytical procedure, not just those that involve c

52、hromatographic techniques. Regardless of the type of analytical procedure, testing should be used to confirm that the system will function correctly independent of the environmental conditions. For example, titration analytical procedures should always include the evaluation of a blank (commonly ref

53、erred to as a blank titration).建議系統(tǒng)適應(yīng)性實驗應(yīng)成為所有分析方法的一局部，而不僅僅是色譜分析方法。無論是哪類分析方法，都要采用實驗來證實該系統(tǒng)能不受 HYPERLINK javascript:; t _self 環(huán)境條件的影響而正確地運行。比方說，滴定法一般來說需要進行空白實驗。F. Preparation of StandardsProcedures for the preparation of all standard solutions (e.g., stock, working standard solutions, internal standard

54、s) should be included.F標(biāo)準(zhǔn)品的制備要有所有標(biāo)準(zhǔn)品溶液比方，儲藏液，工作對照品溶液，內(nèi)部對照品溶液的配制方法。G. Preparation of SamplesSample preparation for individual tests should be clearly described. Specific details should be provided for unusual sample preparations (e.g., solid-phase extraction, derivatization).應(yīng)當(dāng)要按操作步驟對操作過程進行逐步表達。表達應(yīng)當(dāng)要

55、適當(dāng)包括如下信息：平衡時間，樣品進樣順序和系統(tǒng)適應(yīng)性或啟動參數(shù)。需標(biāo)明不常見的危險。I. CalculationsRepresentative calculations, with a tabulation defining all symbols and numerical factors, and specific instructions for the calculation of degradation products and impurities should be included. Any mathematical transformations or formulas us

56、ed in data analysis should be described in detail. These may include logarithmic transformations used to obtain a linear relationship from exponential data, or the use of multiple order regression analyses.I計算應(yīng)當(dāng)要提供代表性計算公式，并要列表說明所有符號和數(shù)字系數(shù)，及計算降解產(chǎn)物和雜質(zhì)的特殊使用說明。所有用于數(shù)據(jù)分析的數(shù)學(xué)轉(zhuǎn)換或公式應(yīng)詳細(xì)描述。這些包括對數(shù)轉(zhuǎn)換以獲得指數(shù)數(shù)據(jù)的線性關(guān)系，或

57、多元回歸分析的使用。J. Reporting of Results1. GeneralThe format used to report results (e.g., percent label claim, weight/weight, weight/volume, parts per million (ppm) including the specific number of significant figures to be reported should be provided.1通那么應(yīng)該規(guī)定關(guān)鍵計算步驟中的數(shù)字單位例如，標(biāo)簽標(biāo)示量的百分比，W/W，W/L，ppm等2. Impuri

58、ties Analytical ProceduresThe name and location/identifier (e.g., retention time (RT), relative retention time (RRT) of impurities and the type of impurity (e.g., process, degradant, excipient degradant) should be included in the analytical procedures for impurities in the drug substance and drug pr

59、oduct. The detection limit (DL) or quantitation limit (QL) should be stated, as appropriate. The DL or QL can be set using the drug substances detection response.2雜質(zhì)分析規(guī)程在有關(guān)原料藥和產(chǎn)品的雜質(zhì)檢測規(guī)程中，應(yīng)當(dāng)包括雜質(zhì)的名稱和檢測位/標(biāo)志例如，保存時間RT，相對保存時間RRT，以及雜質(zhì)的種類比方工藝降解產(chǎn)物，賦形劑降解產(chǎn)物，如有可能，還應(yīng)當(dāng)指明檢測限D(zhuǎn)L或定量限QL。也可以在原料藥檢測中設(shè)置DL和QL。Reporting of

60、organic impurities should cover (1) specified identified impurities by name, (2) specified unidentified impurities by location/identifier, (3) any unspecified impurities, and (4) total impurities. The total organic impurities for the drug product or drug substance is the sum of all impurities equal